Verbal Declarative Memory Dysfunction in Schizophrenia: From Clinical Assessment to Genetics and Brain Mechanisms

The recent literature on the neuropsychology of schizophrenia has emphasized memory deficits as a key area of impairment. Abnormalities in the medial temporal lobe, a brain region crucial for long-term memory formation, have also consistently been reported. We conducted a comprehensive review of verbal declarative memory (VDM) in schizophrenia with the aim of systematically addressing the nature of this impairment. We conclude that verbal declarative memory is significantly impaired in schizophrenia and is largely accounted for by deficits in the encoding stage. Subtle impairments in increased rates of forgetting are present, but are mild compared with those in amnestic disorders. Impairment in other cognitive domains studied thus far (e.g., attention), medication effects, or fluctuations in symptoms do not completely account for the deficit. VDM is among the most impaired neurocognitive domains in schizophrenia (along with attention and executive functions). Milder encoding deficits are present in high-risk subjects and non-psychotic relatives of individuals with schizophrenia suggesting that components of the deficit are associated with a genetic vulnerability to the illness, and are independent of the frank psychotic illness. Furthermore, VDM is observed in individuals experiencing their first-psychotic episode and it remains fairly consistent over time. Preliminary imaging studies and other work suggest abnormalities in prefrontal-hippocampal processing networks. Future work should emphasize delineating specific information processing components contributing to the deficit. This would allow imaging studies to determine which brain regions contribute to specific information processing deficits in schizophrenia.     

阻碍条件性恐惧记忆消退的原因分析

创伤后应激障碍是个体经历严重应激后形成的一种焦虑障碍,对其治疗的关键是消退由创伤应激导致的条件性恐惧记忆,但目前最有效的暴露疗法并不能真正有效地抑制患者恐惧记忆的表达.对条件性恐惧的动物模型研究发现情绪性增强效应、恐惧记忆二级条件化与再巩固、内侧前额叶皮层功能不足等均能够阻碍条件性恐惧记忆的消退.针对这几个方面可以探索治疗创伤后应激障碍的相应方法.     

情绪记忆的神经基础

情绪记忆具有强烈、持久的特点,在记忆中具有优势地位。杏仁核是情绪记忆的关键脑区,其外侧核被认为是情绪回路建立的中心部位。恐惧条件反射是情绪记忆,特别是情绪回路研究的有效手段。情绪记忆的编码,储存与提取受到杏仁核与各相关脑区共同影响,其中激素调节在这些过程中发挥重要作用。文中结合最新的研究成果对情绪记忆的神经机制进行讨论     

相继记忆模式：展现情节记忆形成脑机制的窗口

相继记忆模式在记忆形成的脑认知成像研究领域应用广泛,已成为研究者探究大脑形成记忆时活动的主要窗口。该文在介绍相继记忆模式及记忆形成过程的基础上,分析影响相继记忆效应大小和时空分布的因素,最后讨论内侧颞叶及前额叶神经网络中相关脑区如何分工、协同支持情节记忆形成。情节记忆多维度特性导致该神经网络中有关区域表现出不同形式的相继记忆效应,因此,该文提出有效分离这些脑区在记忆形成中如何分工及交互协同关系进行更为重要     

内侧颞叶与来源记忆

来源记忆不同于项目记忆。早期的研究认为来源记忆的神经基础主要是前额叶,但近几年的相关研究发现内侧颞叶在来源记忆中的作用也是相当重要的,健康被试的功能神经成像研究和内侧颞叶损伤病人研究都为内侧颞叶在来源记忆中的作用提供了可靠证据。     

陈述性记忆存储和巩固的神经机制

综述了陈述性记忆形成和巩固的神经机制,并对经典模型进行了修正和拓展。主要观点是：陈述性记忆的存储和巩固依赖于新皮层不同脑区之间建立新的联系,内侧颞叶在这一过程中起着重要作用;当陈述性记忆完全巩固后,信息的存储和提取完全依赖于新皮质;一个完整的陈述性记忆的信息被分别存储在解剖上分离的语义记忆与情节记忆存储系统内     

状态焦虑对条件恐惧习得和消退的影响

采用44名正常女性大学生作为被试, 通过心理社会压力暴露的方法诱发焦虑组被试的状态焦虑, 采用主观预期值作为指标, 考察焦虑对条件恐惧习得和消退的直接影响, 并探讨这种影响是否也表现在评价性条件作用上。结果表明：心理社会压力暴露显著提高了焦虑组被试的状态焦虑。在习得阶段, 状态焦虑降低了被试对条件刺激的辨别条件恐惧反应, 具体而言, 状态焦虑降低了被试对CS+的主观预期值, 但是却提高了对CS?的主观预期值; 在消退阶段, 状态焦虑抑制了被试对条件刺激的消退。状态焦虑的影响也表现在评价性条件作用上, 和控制组相比, 焦虑组在习惯化和消退阶段对条件刺激表现出了更为负性的效价评定。     

Probing the Brain Substrates of Cognitive Processes Responsible for Context Effects on Recognition Memory

ABSTRACT

Context effects on episodic recognition memory involve separable contributions of target-context binding, additive familiarity, and configural constancy. Here we examine whether these factors reflect contributions of processes attributed to different brain substrates. First, we challenged frontal and medial temporal lobe-based cognitive capacities in healthy young adults, employing divided attention tasks at encoding and retrieval, and extended retrieval delay, respectively. Target-context binding effects were specifically attenuated by delay, but not by divided attention. In a second experiment, older adults were identified by neuropsychological testing as having different levels of frontal and medial temporal lobe-dependent cognitive functions. Consistent with Experiment 1, older adults with low medial temporal lobe function exhibited reduced target-context binding effects, but levels of frontal function did not modulate binding effects. These findings indicate that unlike source memory, context effects on memory are associated with the integrity of medial temporal lobe-based processes but not with the integrity of frontal lobe-based processes. Our findings also emphasize the importance of discriminating between functional subgroups in the attempt to characterize memory processes in older adults.     

干预条件性恐惧记忆表达的相关影响因素分析

创伤后应激障碍是个体经历严重应激后形成的一种焦虑障碍, 对其治疗的关键是熄灭由创伤应激导致的条件性恐惧记忆。条件性恐惧的动物模型研究发现恐惧记忆一旦获得后就难以熄灭, 容易复发, 而这一点也是PTSD的关键临床症状表现之一。因此, 如何更好更持久地熄灭恐惧记忆, 是一个具有重要理论和临床意义的研究热点。本文围绕促进恐惧记忆的长久消退和破坏恐惧记忆的再巩固两方面的行为或药理干预及机制进行综述。针对本文所述的几种基础实验处理, 临床上可以研究治疗创伤后应激障碍的相应疗法。     

条件性恐惧记忆提取消退干预范式

提取消退(retrieval-extinction, Ret+Ext)范式是基于记忆再巩固理论, 利用消退训练(extinction, Ext)能改变条件刺激(conditioned stimulus, CS)的恐惧效价特点, 把消退训练应用到再巩固时间窗内来改写(rewrite)恐惧记忆, 消除恐惧反应。提取消退范式是对传统暴露疗法和药物治疗的创新和拓展, 不仅为创伤性记忆的治疗提供一种非侵入性的技术, 而且也为改写人类记忆、积极心理学探索人类幸福感方面开辟了一种全新的理论视角。     

条件性恐惧记忆消退返回的性别差异

采用预期判断任务考察男女性对已消退的条件性恐惧记忆是否会出现消退返回的现象。结果表明: (1)在对已习得的条件性恐惧记忆消退后4个小时进行测试, 被试整体会出现明显的消退返回现象; (2)对消退返回现象的性别差异进行比较, 女性比男性的消退返回现象更突出, 并且差异显著; (3)与男性相比, 女性对条件性恐惧记忆具有易习得难消退的趋势, 但是性别差异不显著。研究结果验证了消退返回现象存在的普遍性, 并且有着显著的性别差异, 为以后对创伤后应激障碍患者的治疗应考虑性别因素提供了心理学依据。     

前瞻记忆的神经机制：来自临床研究的证据

前瞻记忆是指对预定事件或行为的记忆。本文总结了前瞻记忆脑机制相关的文献,介绍了前额皮层、丘脑,内侧颞叶等脑区域在前瞻记忆中的作用,并通过分析注意缺陷多动障碍儿童、老年痴呆症患者、酒精依赖症和内侧颞叶癫痫患者前瞻记忆的表现,从临床角度深入探讨了前瞻记忆神经机制的问题。证据表明,前额皮层参与前瞻记忆的编码、提取和监控过程,与意向保持也有密切的关系;丘脑与意向的执行有关,并且与前额叶互动在前瞻记忆监控中起着重要的作用;内侧颞叶与编码来源的提取和意向的激活都有密切的关系。研究认为前额皮层在前瞻记忆加工过程中起着核心的作用,同时与丘脑、内侧颞叶等区域相互作用,共同成为前瞻记忆编码、保持、提取、执行的神经基础。     

Fear of routine dental treatment in adults: Its nature and management

Abstract

The fear of dental treatment in adults can be characterised in several ways, loosely related, such as anticipating being afraid, avoiding dental check-ups and seeking treatment only under general anaesthesia. Defined thus, at least a quarter of adults are highly afraid of dentistry. The feared experiences are many, including most frequently, pain. Several studies have shown that anxious patients experience less pain during treatment than they expect. It remains to be confirmed that these are typical experiences because other studies show that local anaesthesia can fail to protect patients from sudden pain in 13% of treatments on average. Expectations of pain are highly resistant to change, the result probably of several influences including distortion in recall of pain-free treatment, intermittent experience of sudden severe pain, expecting pain in order to reduce its impact, and uncertainty about treatment. It has yet to be shown that experience free of discomfort can reduce these expectations. However, relaxation instructions and information about pain management and stop signals can reduce pre-treatment fear. To prevent the onset and the maintenance of anxiety: the prevention of pain is essential; controlled behavioural studies of the treatment of pain and other experiences such as panics are needed. Finally, the need for new instruments to assess all aspects of fear of dentistry is described.     

Memory for between‐list and within‐list information in amnesic patients with temporal lobe and diencephalic lesions

Patients with medial temporal lobe damage and diencephalic damage were compared on two tests of verbal temporal order memory: between‐list discrimination and within‐list discrimination. Both patient groups were impaired relative to a group of healthy control participants. In addition, despite comparable levels of item recognition, the diencephalic group was impaired relative to the medial temporal lobe group on both within‐list and between‐list discrimination. Temporal order memory for between‐list information showed a significant correlation with a composite measure of recognition memory, and the results are discussed in terms of the patients' reliance on familiarity and distance‐based processes to make temporal order judgments.     

情景变换诱发已消退恐惧记忆重现的神经环路

暴露疗法是治疗创伤后应激障碍的主要行为疗法。当被试反复暴露于可引起恐惧反应的条件刺激(如白噪音), 但却不伴有非条件刺激(如足底电击)时, 恐惧记忆将被消退, 形成消退记忆。但恐惧记忆并未从根本上被擦除, 当被试在消退训练以外的情景暴露于条件刺激时, 已消退的恐惧记忆将会重现。海马、内侧前额叶皮层、杏仁核等脑区及其相互连接的神经环路是情景诱发恐惧记忆重现的生理基础。情景变化诱发恐惧记忆重现过程中, 海马可能是通过直接投射至杏仁核基底核、杏仁核外侧核或通过边缘前皮质间接调控杏仁核基底核、杏仁核外侧核的功能, 产生恐惧反应。     

情绪的动机强度与工作记忆任务类型的协调性对自我控制任务的影响

考察趋近动机强度不同的积极情绪和回避动机强度不同的消极情绪与工作记忆的协调性对自我控制任务的影响。结果发现,与高趋近动机的积极情绪、高回避动机的消极情绪以及中性情绪相比,在低趋近动机的积极情绪下完成言语工作记忆以及在低回避动机的消极情绪下完成空间工作记忆,工作记忆成绩提高,而Stroop分数降低,这表明情绪与工作记忆的协调性受到情绪动机强度的影响。     

人类记忆再巩固研究现状及临床应用

巩固的记忆被提取后,进入不稳定状态,再重新稳定下来,这个过程称为记忆再巩固。本文首先阐述人类记忆再巩固主要研究方法和经典范式,梳理记忆再巩固在人类恐惧记忆和情景记忆两个方面的相关研究,并从认知神经科学角度整理记忆再巩固的加工机制。然后总结记忆再巩固应用于创伤性应激障碍和药物成瘾等心理障碍临床治疗的相关文献。最后本文提出未来研究的方向和建议,希冀对人类记忆再巩固的理论研究和临床应用提供新思路。     

内侧颞叶系统在知觉启动中的作用及其机制

以ll例内侧颞叶(MTL)损伤病人为被试,探讨MTL与知觉启动的关系及其内在机制。被试依次完成学习颜色词、快速词命名和再认任务。在实验l的词命名中包括旧词、重组颜色词和新词,结果表明,MTL损伤病人没有表现出旧词的命名时间短于重组颜色词的现象,颜色启动效应受损,其再认成绩也低于正常被试。但是当用新颜色词代替重组颜色词后(实验2),MTL损伤病人读旧词的时间明显短于新颜色词,颜色启动与正常对照组之间没有明显差别,但他们的再认成绩仍比对照组低。这表明,当任务要求被试加工项目与其特性之间的关系时(词与颜色),MTL损伤对启动效应会有影响,提示MTL在一些形式的知觉启动中起重要作用。